The Risk Factors Of Recurrence Unprovoked Venous Thromboembolism And Meta Analysis Effciency And Safety Of Oral Anticoagulants On Extended Treatment Of Unprovoked Venous Thromboembolism

Objective Venous thromboembolism(VTE) is one of the most health-threatening diseases in the world With annual incidence of 0.1% to 0.27% [1].The incidence of unprovoked VTE varies between 25% and 50% in all venous thromboembolism disease.The incidence of recurrence unprovoked VTE is high. In the first year, the recurrence rate is 5% to 27%,the fatality rate approaching 5% to 13%.10 years cumulative recurrence rate can as high as 50%[1, 2]. The ACCP guideline did not make clear a regulation for unprovoked VTE patients of what are risk factors of recurrence and how long the anticoagulation to use. The main purpose of this study is to explore risk factors for unprovoked VTE recurrence, and to examine and compare the efficacy and safety of oral anticoagulant drugs used in the extended treatment of unprovoked VTE.We aim at to early diagnosis the recurrence of unprovoked VTE and guiding the clinical application.Method Part One: From January 2012 to December 2015, collecting unprovoked VTE patients clinic date,The patients were in accordance with the inclusive criteria who can meet the diagnostic criteria made by American College of Chest Physicians(ACCP) [3].The patients were excluded who meet the exception of standard criteria.All patients were given anticoagulation, The clinic date included: patients’ general information(gender, age, height, weight, body mess index), signs, basic diseases(coronary heart disease, chronic obstructive pulmonary disese), imaging diagnosis method, the initial diagnosis(PE, DVT or PE + DVT), initial treatment, biological indicatiors(D – D, FIB, WBC, HB), the follow-up period of clinical symptoms, signs, imaging and biological indicatiors, the application of anticoagulant drugs. All patients were divided into recurrence group and non recurrence group. All date was analyzed with SPSS statistical software. With P<0.05 the difference was statistically significant.The factors that influence recurrence of unprovoked VTE were studied using logistic regression model. Part Two: Make the objective, inclusion, exclusion criteria and search strategies.The search was conducted through Pubmed and Embase, the Cochrane library data Chinese National Knowledgey Ifrastructure,Wan Fang data,Weip Data-base manual retrieval system evaluation related references as a supplement for randomized clinical trial on oral anticoagulants for extended treatment of unprovoked VTE. Two authors independently extracted information from each eligible study. The statistical software Rev Man5.3 and ITC was used to estimate relative risk ratios(RR) and to produce forest plots along with the assessment of the heterogeneity between the studies, the results was presented with forest plots, RR and 95% confidence interval.Results Part One: 206 unprovoked VTE patients were included in this study, with 129 men, 77 women, average age(52.45+13.36).24 patients in recurrence group, the non recurrence group had 182 patients. Single factor analysis show that BMI, D- D, FIB had statistically significant difference(p<0.05), Other factors have no statistically significant between-group difference were detected.Logistic regression show that BMI(OR 2.33 95% CI 1.14-4.74, P = 0.02); D – D(OR 3.02 95% CI 1.41- 6.51 P = 0.003); FIB(OR 2.17, 95% CI 1.30 4.88 P = 0.004) were risk factors for recurrence of unprovoked VTE. Part Two:5 articles were included in the Meta – analysis.Meta results showed that on extended treatment period, oral anticoagulants is superior to placebo in efficacy(RR0.16 95% CI(0.12 0.22),P < 0.00001).subgroup analysis revealed that the NOAC(RR 0.17 95%CI 0.12-0.24,P<0.00001) and warfarin(RR 0.10 95%CI 0.04-0.27 P<0.00001)decreased the incidence of recurrence than the placebo. In security, anticoagulants compared to placebo do not increased risk of major bleeding(RR 1.60,95%CI 0.51-5.0,P=0.42). NOAC compared to warfarin decrease the risk of major bleeding(RR0.251 95%CI0.027-2.319 P<0.001).anticoagulants compared to placebo increased risk of clinically relevant bleeding(RR 2.34 95%CI 1.51-3.64, P=0.0001)) subgroup analysis revealed that the NOAC( RR 2.21 95%CI 1.36-3.60,P=0.001) and warfarin(RR5.11 95%CI 1.13-23.14,P<0.03)increased the incidence of clinically relevant bleeding. NOAC compared to warfarin decrease the risk of clinically relevant bleeding( RR0.089 95%CI 0.018-0.433 P=0.0254).NOAC compare to palebo decreased the incidence of Cardiovascular event(RR 0.44 95%CI 0.21-0.91,P=0.03).Conclusion Part One: BMI(OR2.33 95% CI1.14-4.74 P = 0.02); D- D(OR3.02 95% CI1.41-6.51 P = 0.003) FIB(OR2.17 95% CI 1.30 4.88 P = 0.004) were the risk factors for unprovoked VTE recurrence which could be used as predictors of unprovoked VTE recurrence. Part Two: In efficacy oral anticoagulants decreased the risk of recurrence(RR0.16, 95% CI 0.12 0.22, P < 0.00001). In security, anticoagulants compared to placebo did not increased the risk of major bleeding(RR1.60 95%CI 0.51-5.0,P=0.42) increased the risk of clinically relevant bleeding(RR2.34 95%CI 1.51-3.64, P=0.0001). NOAC compare to warfarin decreased the risk of major bleeding( RR0.251 95%CI 0.027-2.369 P<0.0001) and clinically relevant bleeding(RR0.089 95%CI 0.018-0.433 P=0.0254).NOAC compare to palebo decreased the incidence of Cardiovascular event(RR 0.44 95%CI 0.21-0.91,P=0.03).Oral anticoagulants should be used on the extended treatment of unprovoked VTE and new oral anticoagulants may be a choice.